Lower extremity ulcers (LEUs) are very common with an estimated prevalence of 1 to 2% among US adults and important effect on public health. SUIs are divided into two groups: leg ulcers and foot ulcers, due to differences in causes, pathogenesis and treatment. Even with the best care currently available, 25% to 50% of leg ulcers and more than 30% of foot ulcers are not completely healed after 6 months of treatment.
About 70% of leg ulcers are caused by venous disease, and almost 20% are due to arterial insufficiency or mixed arteriovenous disease. Approximately 85% of foot ulcers are caused by peripheral neuropathy, often complicated by arterial disease.
Risk factors for venous leg ulcers are: older age, female sex, family history of venous leg ulcer, white race, history of deep vein thrombosis or phlebitis, previous leg injury, chronic leg edema , sedentary lifestyle and prolonged standing.
The risk factors for any arterial ulcer are: diabetes mellitus, hypertension, hyperlipidemia, obesity and smoking. Risk factors for foot ulcers include lack of sensation, limited joint mobility, anatomical abnormalities, diabetes mellitus, vascular disease, and repetitive increases in local pressure.
Patients with venous leg ulcers require more medical resources than patients in a demographically comparable control population. They also miss work days due to ulcer-related complications or the need for follow-up.
These circumstances result in higher job loss costs that are almost one-third higher than those of a combined population. Patients with diabetic foot ulcers are hospitalized more frequently, require more home health care, and make more visits to the emergency department and outpatient clinics than patients in a combined population.
Because some recommendations are based on the findings of small observational studies or expert opinion, the authors warn of disagreement regarding some recommended approaches; However, they say, “the approach we propose here has proven to be useful in our medical practice.”
Physiopathological characteristics of ulcer types
♦ Venous ulcers
When the valves in the leg veins are damaged or the veins are dilated, retrograde blood flow and venous hypertension occur. Sustained ambulatory venous pressure causes removal of edema-causing fluid and proteins and red blood cell extravasation, which in turn results in hemosiderin deposition and pigmentation.
Mechanical disruption of endothelial cells and their glycocalyx coverage causes leukocyte marginalization and activation, leading to persistent inflammation and oxidative stress, along with the expression of multiple cytokines and chemokines. Excessive expression of matrix metalloproteinases alters collagen renewal and causes the destruction of dermal tissues and subsequent ulcer formation.
The pericapillary fibrin deposition traps growth factors and disrupts oxygen diffusion, thus contributing to local tissue hypoxia. The end result is an open, draining wound with overlapping slough and surrounding induration.
♦ Arterial ulcers
Arterial ulcers are the result of impaired tissue perfusion. In addition to intramural restriction of blood flow, extramural strangulation and mural thickening also contribute to reduced perfusion.
Causes of reduced arterial blood flow are atherosclerotic peripheral vascular disease, macro- and microvascular disease due to diabetes mellitus, vasculitis, and microthrombi. Reduced perfusion of the skin and soft tissues causes ischemia and subsequent necrosis leading to ulceration of the leg. Recurrent episodes of ischemia and reperfusion also contribute to tissue injury.
♦ Diabetic ulcers
The causes of diabetic foot ulcers are multifactorial and include arterial insufficiency and neuropathy, which confer a predisposition to injury and ulcer formation. The loss of protective sensation in patients with diabetes makes them vulnerable to physical trauma and therefore, meticulous foot care and frequent inspection of their feet should be done in patients with diabetes.
Sweating deficiency and impaired foot perfusion cause skin dryness, which facilitates skin lesions following minimal repetitive trauma. Autonomic neuropathy leads to foot deformities (e.g., Charcot foot) resulting from pressure on prominent areas of the foot. Other abnormalities related to diabetes mellitus (such as defective leukocyte function) impair wound healing and lead to perpetuation of ulcers and secondary infection.
♦ Pressure ulcers
Pressure ulcers are caused by constant pressure on bony prominences such as the heel, and usually develop in non-ambulatory patients. Prolonged tissue compression along with friction and shear produces local tissue ischemia and necrosis, leading to ulcer formation. ?
Diagnosis
♦ Identification of the type of ulcer
Most types of ulcers can be identified based on their appearance and location. A history should be taken focusing on coexisting medical conditions, such as diabetes mellitus, peripheral arterial disease, and deep vein thrombosis, which may provide a clue to the underlying cause of the ulcer. In addition to an examination of the wound and surrounding skin, the physical examination should include a neurovascular evaluation to identify neuropathy and arterial insufficiency.
♦ Venous ulcers
Typically, venous leg ulcers occur over the medial aspect of the leg between the lower calf and the medial malleolus, accompanied by edema, pigmentation (combined hemosiderin and melanin), venous dermatitis, white atrophy (porcelain-white scars , telangiectasia and pigmentation) and lipodermatosclerosis.
Patients often report pain or a burning sensation (or both) and swelling in the leg, which increases during the day and decreases with elevation of the leg. The patient’s history may also reveal deep vein thrombosis, trauma, or surgery to the affected leg. Venous leg ulcers are superficial and irregular in shape, and contain granulation tissue or yellow fibrin. Venous reflux can be diagnosed using Doppler ultrasound of the leg.
♦ Arterial ulcers
Arterial ulcers are more common among smokers and patients with diabetes mellitus, hyperlipidemia, and hypertension. Patients may have a history of intermittent claudication or pain at rest that worsens when the leg is elevated and decreases when the leg is hanging. Arterial ulcers may involve the distal part of the foot, in areas of trauma (eg, toes and heels) and the anterior aspect of the leg where there is no arterial redundancy.
Ulcers are often dry and appear "perforated" with well-demarcated borders and a pale, non-granulated, necrotic base. Arterial ulcers can also be very deep. Abnormal pedal pulses, coldness in a single leg or foot, a prolonged venous filling time, and the presence of a femoral murmur lean the diagnosis toward peripheral arterial disease.
Delayed capillary refill and discoloration, skin atrophy, and lack of foot hair may not be helpful in establishing a diagnosis. An ischemic foot is sometimes pink and relatively warm due to arteriovenous shunts. Elevating the leg may worsen the pain because blood drains and the foot becomes pale (elevation pallor). Delayed return of red color or prolonged venous filling when the leg is hanging may also be a sign of decreased perfusion.
In addition to palpation of arterial pulses in the leg and foot, a simple method to identify decreased lower extremity perfusion is measurement of the ankle-brachial index (ABI). Measurements are performed with a standard blood pressure cuff and an EchoDoppler device. An index <0.9 indicates arterial insufficiency and is an indicator of further investigation by a vascular surgeon. Lower IBTs are associated with more severe vascular disease, and ratios <0.5 are often seen in patients with ulcers that developed as a result of arterial insufficiency.
Falsely normal or even elevated IBT can be observed in patients with non-compressible vessels, patients with diabetes caused by blood vessel glycation, and in elderly patients with vascular calcification. When the diagnosis is unclear, computed tomography angiography and magnetic resonance angiography can be used. Transcutaneous oxygen tension (oxygen level of the tissue under the skin), when it can be measured, is a good indicator of limb ischemia.
A recent meta-analysis showed that a transcutaneous oxygen tension of 20 mm Hg was a valid cutoff value for predicting the need for limb amputation and that a transcutaneous oxygen tension of 30 mm Hg was an appropriate value for predicting healing of the limb. wound after limb amputation.
♦ Neuropathic diabetic ulcers
Neuropathy usually occurs in patients with diabetes mellitus and is a major risk factor for foot ulceration. Blood glucose (or glycated hemoglobin) can be used to evaluate hyperglycemia, and to evaluate neuropathy, sensation examination of the legs and feet should be performed. Neuropathic ulcers are usually located at sites of trauma (often repetitive) or at sites of prolonged pressure, such as the tip of the toe (e.g., hammertoe), the medial side of the first phalanx of the metatarsal joint or the plantar surface of the feet.
A simple assessment using a 10 g filament as a measure of the foot’s ability to detect sensation has been validated, regardless of whether the assessment is made of the foot’s ability to perceive the vibration of a standard tuning fork. Testing for neuropathy should not be done on areas where there are calluses.
♦ Pressure ulcers
Pressure ulcers occur due to the inability to feel (e.g., neuropathy) or relieve (e.g., weakening) prolonged pressure on the skin, typically on the heel. Skin atrophy and loss of muscle mass, common conditions in debilitated patients, further contribute to susceptibility to pressure ulcer formation.
Identifying the infection
Although it may be difficult, recognition of infection in IEUs is essential. Of all UEIs, diabetic foot ulcers are the most prone to infection; In more than half the infection is clinical at the time the patient presents to a health professional. Early identification of infection in diabetic foot ulcers is critical, because 1 in 5 patients with an infected foot ultimately undergo amputation.
The diagnosis of infection is clinical and should not be based on swab findings from the wound surface. Microbiological findings support and guide antibiotic therapy. Signs and symptoms of localized infection include local warmth, erythema, tenderness or pain, swelling, and purulent discharge. Systemic infection and subsequent host response are manifested by fever, chills, leukocytosis, spreading erythema, and lymphangitis.
If initial antibiotic treatment is unsuccessful, deep wound swabbing, aspiration of purulent secretion, and tissue biopsy can help identify the causative agent and choose antibiotic therapy. Most acute infections that have not been treated with antibiotics are caused by gram-positive organisms such as staphylococci.
Chronic infections, especially after antibiotic administration, are generally polymicrobial, with gram-positive, gram-negative, and anaerobic bacteria. Severe necrotizing infections are characterized by the presence of crackles, blisters, and extensive necrosis, warranting urgent consultation with a vascular surgeon. Underlying osteomyelitis is not uncommon in diabetic foot ulcers and should be suspected in the case of deep, chronic ulcers on the bones. A sterile blunt metal probe can be inserted deep into the wound.
In hospitalized patients, osteomyelitis can be diagnosed with greater predictive value by identifying the bone at the depth of the ulcer (hard grit sensation). Although the standard criterion for diagnosing osteomyelitis is bone biopsy, infections can be confirmed by non-invasive methods such as plain radiography or magnetic resonance imaging, which is more sensitive than plain radiography.
Treatment
♦ General principles
There are a number of guidelines for managing UEIs. General principles include wound debridement, infection control, dressing application, localized pressure relief, and treatment of underlying conditions such as diabetes mellitus and peripheral arterial disease. Lifestyle changes (eg, smoking cessation and diet modification) should also be made to help manage underlying conditions.
♦ Debridement of wounds
Debridement, which involves the removal of devitalized tissue, reduces the bacterial load. The most rapid method is to perform careful surgical debridement (using a scalpel, sharp scissors, or both) to viable bleeding tissue, with removal of senescent fibroblasts from the wound bed and phenotypically and genotypically abnormal keratinocytes from the wound edge. . Autolytic dressings (alginates, hydrocolloids, hydrogels) and enzymatic agents (collagenase) can also be used. Although these options are slower than surgical debridement and less painful and traumatic.
♦ Infection control
A systematic review of 45 randomized controlled trials of 4,486 patients showed no evidence supporting the routine use of systemic antibiotic prophylaxis for SUIs. Although the review showed evidence supporting the topical use of iodinated cadexomer, there is no evidence supporting the prolonged or routine use of silver or honey-based products on non-infected wounds. “In our practice,” the authors say, “we use topical iodinated cardexomer for contaminated ulcers without clear evidence of infection and as an adjunct to systemic antibiotic therapy in infected ulcers.”
If infection is suspected due to the presence of malodorous purulent discharge, or because healing is not achieved after routine debridement, infection can be confirmed by tissue biopsies (if available) or quantitatively validated wound swabbing (not necessary when infection is obvious).
For ulcers that have a high bacterial load (>106 colony-forming units/gram of tissue, or any level of β-hemolytic streptococci) after adequate debridement, topical or systemic antibiotic therapy against gram-positive bacteria, such as dicloxacillin, cephalexin or clindamycin. “In our practice,” they note, “topical antibiotics are used first, unless there is evidence of obvious infection.”
Due to the multibacterial causes in patients with diabetes, broad-spectrum systemic antibiotics that cover gram-positive and gram-negative bacteria as well as anaerobic organisms should be used. Possible agents are the combination of a penicillin and a ß-lactamase inhibitor or a fluoroquinolone or linezolid alone.
Patients with disseminated cellulitis erythema or clinically significant evidence of systemic infection (e.g., fever, chills, or lymphangitis), or patients with coexisting clinically significant medical conditions or immunocompromised patients (uncontrolled diabetes mellitus or use of systemic glucocorticoids) and Patients with infection that worsens or does not respond to oral antibiotic agents should generally receive intravenous antibiotics. For refractory or complex infections, it is advisable to consult an infectious disease specialist.
♦ Wound dressing
Dressings that promote an adequate level of moisture (while limiting maceration) and protect the ulcer from further injuries and cuts should be used to treat wounds. There are a large number of wound dressings, such as hydrocolloids, alginates and foams. Many bandages can be left in place for up to 1 week unless they are smelly or saturated with exudate. The decision about what type of bandage to use is based on the preferences of the patient and the professional.
In general, dry wounds are treated with moisture-promoting bandages, while exudative wounds should be managed with absorbent bandages. Bandages also come in combination with antiseptic agents (e.g., silver nanoparticles); which may be useful in the short term to reduce the concentration of bacteria when there is infection, but are not recommended for long-term use. Foam dressings, despite their frequent use, are no more effective than other standard dressings.
♦ Pressure relievers
To prevent and treat pressure ulcers, it is very important to avoid or minimize pressure on the bone. Proactive pressure ulcer risk assessment (Braden scale) should be performed in all hospitalized patients. Frequent repositioning, use of pressure-reducing surfaces (eg, an alternating pressure mattress), and orthotics that relieve ulcer pressure are important to minimize damage.
Specific therapies based on the type of ulcer
♦ Venous ulcers
Compression therapy is highly recommended for venous leg ulcers. The compression bandage is applied from the toes to the knees and should include the heel. Graduated pressure is applied, with more pressure at the distal end. Each successive wrapper must overlap the previous one by 50%. Several major clinical trials and systematic reviews have concluded that compressive therapy, compared with non-compressive therapy, promotes healing of venous leg ulcers and reduces the risk of recurrence, being similar to surgical intervention.
Multicomponent systems containing an elastic bandage appear to be more effective than those containing only non-elastic components. For the treatment of venous leg ulcers with varicose veins, post-thrombotic syndrome or lymphedema, compression pressures between 30 and 40 mm Hg are recommended. In their practice, the authors use a modified compression therapy for patients with mild to moderate arterial disease (e.g., IBT between 0.5 and 0.8) by applying non-elastic bandage or reducing the number of compression layers and make a weekly monitoring of patients to ensure that arterial flow is adequate.
In severe cases (OBY <0.5) compression is not indicated because it can further reduce arterial flow. Venous ablation appears to reduce the incidence of recurrence and may facilitate healing of venous leg ulcers, although evidence from well-conducted studies is still lacking. A meta-analysis of studies that included patients with venous leg ulcers showed that 45% of all ulcers are due to superficial venous reflux alone, while 88% of venous leg ulcer patients have reflux in the system. superficial.
Superficial vein reflux can be treated on an outpatient basis with procedures such as sclerotherapy or laser or radiofrequency venous ablation. Because of the concept that inflammation plays a role in the pathogenesis of venous leg ulcers, two small randomized controlled trials evaluated the effectiveness of adding a dose of 300 mg/day of oral aspirin to compression, which led to beneficial results. However, the small sample size and related problems for study quality (short follow-up and poor description of placebo) limit the ability to reach conclusions regarding the benefits and harms of regular aspirin use in these cases. .
The authors prescribe aspirin to patients with venous leg ulcers when it is not contraindicated. Despite the lack of data from randomized controlled trials, split-thickness autologous skin grafting is often used to debride chronic noninfected nonhealing IEUs, especially venous leg ulcers, with a success rate of up to 90% at 5 years.
Because surgery (e.g., vein ligation and stripping) has been shown to reduce the incidence of recurrence of venous leg ulcers, patients with chronic UEIs who have not healed despite debridement should be referred. to a vascular surgeon to consider venous intervention. For venous leg ulcers caused by small varicose veins other than the saphenous type, intravenous intervention may be used along with compression.
♦ Arterial ulcers
The most effective method to accelerate the healing of arterial ulcers is to restore local blood flow through revascularization. A systematic review of the effectiveness of revascularization for foot ulcers using endovascular therapies or bypass surgical techniques, or in patients with diabetes mellitus and peripheral arterial disease concluded that there were insufficient data to recommend one method of revascularization over another. The decision to perform an endovascular procedure or open bypass surgery should be based on the patient’s characteristics and preferences, as well as the surgeon’s experience and preferences.
♦ Diabetic and pressure ulcers of neuropathic origin
Careful inspection of the patient’s footwear can help identify improper fit, wear, or the presence of foreign bodies that contribute to ulcer formation. Pressure relief is essential in neuropathic ulcers and can be achieved with the use of full contact casts (i.e., non-removable casts), removable boots, instant full contact cylinders (i.e., removable displacement cylinders). which become non-removable due to the addition of plaster), fiberglass boots and wheelchairs and, to a lesser extent, with healing sandals, crutches and walkers.
In two meta-analyses, non-removable methods (full contact molds or instant full contact molds) were more effective in healing plantar ulcers than removable methods. The use of specialized systems that measure shock pressure while the patient walks barefoot or with shoes can help tailor treatment. Patients should also be referred to a foot and ankle specialist to consider correction of any bony abnormalities. However, many surgical offloading procedures are more effective at preventing ulcers than active ulcers.
♦ Advanced treatments
If a wound does not respond to standard care (with a response typically defined as a 30% reduction in wound size for venous leg ulcers and 50% reduction in wound size for diabetic foot ulcers, within 4 weeks) at the start of treatment), referral to a wound specialist is indicated.
For venous leg ulcers, complementary treatments can be considered that in order to accelerate healing include oral medications such as pentoxifylline, aspirin, simvastatin and sulodexide, as well as cell and tissue-based products such as skin construct living bilayer, the porcine submucosa of the small intestine, a synthetic matrix made of poly-N-acetyl glucosamine or granulocyte-macrophage colony-stimulating factor.
Adjunctive therapies that may be applied to diabetic foot ulcers include platelet-derived growth factor, platelet-rich plasma, placental membranes, human amyotic membrane, bilayer skin equivalent, dermal skin substitutes, Negative pressure wound therapy and hyperbaric oxygen therapy. Other promising therapies include ultrasound, electrical stimulation, extracorporeal shock wave therapy, and spinal cord stimulation.
Patient location
Patients with any limb- or life-threatening condition should be hospitalized and evaluated by a vascular surgeon or wound specialist. Patients with systemic infection and those with expanded local infection that does not respond to oral antibiotics should be hospitalized to receive intravenous antibiotics.
Patients who are dependent or unable to care for wounds may require home confinement or confinement to a skilled nursing facility or hospital. All other patients can be treated with wound dressing and pressure relief (when indicated) and referred to their primary care physician or wound specialist.
The intervention of an orthopedist should also be considered to evaluate the use of an orthopedic shoe as a preventive measure. Finally, given the burden of UEI, healthcare professionals should focus not only on early intervention but also on prevention in patients at risk for UEI.
